Patients' opinions of the use of psychiatric case-finding questionnaires in general practice

Background The common mental disorders of depression and anxiety often remain undetected in general practice. Psychiatric screening instruments have been recommended to assist detection. Aim To assess patients' attitudes towards the use of psychiatric screening questionnaires for common mental disorders within general practice. Design Twenty focus groups comprising 127 patients were conducted in Wales, UK. The groups were distinguished by age, sex and locality. Results The majority of respondents felt that the use of a screening questionnaire was acceptable and would be willing to complete one within a general practice setting. However, a number of individuals expressed concern about the validity of the kinds of questions asked and the usefulness of the instrument in practice. Respondents also discussed their concerns relating to issues of confidentiality and the doctor's response to the assessment. Conclusion The study indicates that lay beliefs towards mental illness, particularly relating to perceived stigma, will continue to pose problems for the routine use of psychiatric case‐finding questionnaires within general practice.     

Overexpression of protease inhibitor-dead secretory leukocyte protease inhibitor causes more aggressive ovarian cancer in vitro and in vivo

The alarm anti-protease secretory leukocyte protease inhibitor (SLPI) is frequently overexpressed in ovarian cancer cells and has been proposed for inclusion in biomarker panels but function remains unclear. We hypothesized that SLPI overexpression promotes ovarian cancer growth and survival. Low SLPI-expressing Hey-A8 ovarian cancer cells were engineered to produce functional (WT) or protease inhibitor-null (PI-) mutant SLPI; lack of PI activity was confirmed by enzymatic assay. WT/SLPI and PI- mutants stimulated significant proliferation and survival of Hey-A8 ovarian cancer cells under basal culture conditions ( P ≤ 0.02), in soft agar colony number and size ( P ≤ 0.05), and in anoikis resistance ( P ≤ 0.005). SLPI protected the ovarian cancer survival factor, progranulin (PRGN), and HEY-A8 cells from degradation and apoptosis due to neutrophil elastase. PI-/SLPI cells had greater protective activity than WT/SLPI cells. HEY-A8 murine xenografts revealed enhanced solid tumor formation, dissemination, and invasion in WT/SLPI and PI-/SLPI mutants. Increased proliferation was demonstrated by Ki-67 staining ( P ≤ 0.02). Increased secreted PRGN was seen in culture and was also observed by immunohistochemistry in the SLPI transfectant xenografts. This study describes a PI-independent function for SLPI in ovarian cancer growth and dissemination. ( Cancer Sci 2009; 100: 434–440).     

Toxic effects of drugs used in the ICU. Antiarrhythmic agents

Supraventricular and ventricular arrhythmias remain relatively commonplace in the ICU. Proper pharmacologic treatment requires that the clinician recognize accompanying disease states that may alter the pharmacokinetics and pharmacodynamics of antiarrhythmic drugs. In addition, knowledge of cardiovascular toxicity, noncardiovascular adverse effects, and drug-drug interactions are necessary to optimize antiarrhythmic drug therapy.     

Imaging immune surveillance by T cells and NK cells

Summary: As T cells and natural killer (NK) cells survey the surface of other cells, cognate receptors and ligands are commonly organized into distinct micrometer‐scale domains at the intercellular contact, creating an immune or immunological synapse (IS). We aim to address the still unanswered questions of how this organization of proteins aids immune surveillance and how these domains are biophysically constructed. Molecular mechanisms for the formation of the IS include a role for the cytoskeleton, segregation of proteins according to the size of their extracellular domains, and association of proteins with lipid rafts. Towards understanding the function of the IS, it is instructive to compare and contrast the supramolecular organization of proteins at the inhibitory and activating NK cell IS with that at the activating T cell IS. Finally, it is essential to develop new technologies for probing molecular recognition at cell surfaces. Imaging parameters other than fluorescence intensity, such as the lifetime of the fluorophore's excited state, could be used to report on protein environments.